title: Systemic treatment with the sphingosine-1-phosphate analog FTY720 does not improve fracture healing in mice.
abstract: Sphingosine-1-phosphate (S1P) has recently been recognized as a crucial coupling molecule of osteoclast and osteoblast activity provoking osteoanabolic effects. Targeting S1P receptors could, therefore, be a potential strategy to support bone formation in osteopenic diseases or in fracture repair. Here we investigated whether systemic treatment with the S1P analog FTY720 (Fingolimod) could improve fracture healing. Twelve-week-old, female C57BL/6 mice received an osteotomy of the femur, which was stabilized using an external fixator. The mice received a daily subcutaneous injection of either FTY720 (6 mg/kg) or vehicle from the third postoperative day. Fracture healing was evaluated after 10 and 21 days using biomechanical testing, µ-computed tomography, and histomorphometry. Because FTY720 is supposed to influence osteoclast recruitment, osteoclasts were identified in the fracture callus by staining for tartrate resistant acid phosphatase (TRAP). There were no significant differences in callus mechanical properties, tissue composition and osteoclast number between the groups, suggesting that systemically applied FTY720 did not influence bone regeneration in this model of regular fracture healing. Even if further studies should test the potency of FTY720 under unfavorable healing conditions, we conclude that the effect of systemically applied FTY720 on fracture healing might be inferior compared to other anabolic treatments. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1845-1850, 2013.
authors.affiliation: Institute of Orthopaedic Research and Biomechanics, Center of Musculoskeletal Research, University of Ulm, Ulm, Germany.
authors.forename: Aline
authors.initials: A
authors.lastname: Heilmann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schinke
authors.forename: Ronny
authors.initials: R
authors.lastname: Bindl
authors.forename: Tim
authors.initials: T
authors.lastname: Wehner
authors.forename: Anna
authors.initials: A
authors.lastname: Rapp
authors.forename: Melanie
authors.initials: M
authors.lastname: Haffner-Luntzer
authors.forename: Astrid
authors.initials: A
authors.lastname: Liedert
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D001861:Bone Regeneration / Q000187:drug effects; D005260:Female; D000068876:Fingolimod Hydrochloride; D017102:Fracture Healing / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D011409:Propylene Glycols / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D011409:Propylene Glycols; D000135:Acid Phosphatase; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: FTY720; fracture healing; sphingosine-1-phosphate